Chemical Process Safety

Determine the Safety of Chemical Processes Prior to Scale-up

Chemical Process Safety

Ensure Your Chemical Process Is Safe

Chemical process safety is concerned with ensuring that the energy released by the reaction can be safely removed from the reactor without the risk of thermal runaway or explosion. Simple at the laboratory scale, it becomes progressively more difficult throughout scale-up, due to the changing ratio of heat removal capacity to reactor volume. Thus, an exothermic process which runs safely in the laboratory may be spectacularly unsafe to run at plant scale. It is critical to fully understand the risks inherent in moving to the larger scale before manufacturing begins. The use of reaction calorimetry is an essential part of process development studies, providing detailed information about the rate of heat production. This allows researchers to optimize the temperature and dosing profiles to maximize the safety of the process at all times, and reduce to a minimum the risks involved.

Reaction Calorimetry

Comprehensive Heat Analysis

A reaction calorimeter is used to study a chemical process at laboratory scale in order to characterize the true rate of heat production, and understand how it may be influenced by process parameters such as temperature, mixing, and reagent concentration. By mapping the full reaction space, the safest process conditions can be identified. Researchers then can adapt the process to ensure it only operates within the boundaries that minimize risk. Reaction Calorimetry also allows researchers to safely explore conditions that may lead to a process upset, and determine the consequences of out-of-limits operation.

Understand the Risks of Chemical Processes

Reaction Calorimetry Applications

The hazard potential and risk of chemical processes are related to reactivity of chemicals involved and the process design itself. The appropriate design of a process is essential to keep the reaction under control at any given time. Striving for an intrinsically safe process is thus the goal of process development

Avoid Incidents at Scale-up

Considering an exothermal reaction, the worst case scenario is a total failure of cooling. If this occurs, risks include adiabatic temperature rise driven by the synthesis reaction and accumulated energy, potential process emergency if the boiling point is reached, and thermal decomposition leading to secondary reactions and explosion.

Process Safety by Design

In the semi-batch reaction to the left, the reactant is added during a temperature ramp. The overlapping effects (temperature ramp, reactant addition, and the reaction itself) require an accurate determination of the heat flow across the reactor wall, the heat accumulation, and the energy needed to adjust the temperature of the added reactant. This places high demands on the measuring system in terms of accuracy and data evaluation. Caution should be exercised when choosing a calorimeter to be sure it can provide these values, especially under non-isothermal conditions.

Using Micro-Calorimetry and DSC

Reactions can liberate a significant amount of energy, and if this is not removed from the system, the temperature can increase up to the point where a thermal decomposition occurs. This can lead to a thermal runaway and explosion. Before any process is operated at scale, it is essential to study the relative stability of the materials and understand the risk of exothermic decomposition. Micro-calorimetry tools, such as differential scanning calorimetry (DSC), can quickly and easily provide an early indication of thermal instability. A series of isothermal experiments of a reaction mixture are shown thermal measuring the behavior at different temperatures. The heat evolution signals are use to calculate the adiabatic runaway potential and timeframe under which it would occur.

Reaction Calorimetry in Practice

Related Content and Solutions

METTLER TOLEDO Reaction Calorimeters have been used in Chemical Process Safety laboratories for more than 30 years. Our Publications Library contains a range of presentations, case studies and examples provided by our customers from across the chemical, pharmaceutical and polymer industries.

From 100 mL to 2 L

METTLER TOLEDO manufactures a range of reaction calorimeter systems for use at any stage of chemical process development. EasyMax HFCal is ideal for use in early-stage development, and provides critical thermal data from a 100 mL scale reaction. OptiMax HFCal operates at the 1 L scale, and is ideal for use in process development and scale-up laboratories. RC1mx is the gold standard for the process safety laboratory, where it has been the reference system for more than 30 years.

Scaling-up a chemical process from lab to manufacturing gives useful results only with accurate heat transfer coefficients. Measuring the jacket and reactor temperature (during the release of a well-defined amount of heat) allows researchers to accurately compute the thermal resistance which is used to model the heat transfer and make critical predictions for reactors at larger scale. Reaction calorimetry is essential to determine parameters that impact the heat transfer and the heat transfer coefficients to develop models to maximize the bandwidth of a manufacturing plant.

Mixing in a Chemical Reactor and the Effect on Reaction Kinetics and Scale-up

Mixing is the reduction or elimination of inhomogeneity of phases that are either miscible or immiscible. Process scale-up and optimization require that the impact of mixing on the reaction rate be quantified. Automated, controlled experiments can be run in parallel in a laboratory reactor system to establish a mass transfer correlation, and provide a means to quickly adjust the gas/ liquid interface area and reactor volume. This achieves the desired conditions required for the scale-up or scale-down of a process.

In situ chemical reaction kinetics studies provide an improved understanding of reaction mechanism and pathway by providing concentration dependences of reacting components in real-time. Continuous data over the course of a reaction allows for the calculation of rate laws with fewer experiments due to the comprehensive nature of the data. Reaction Progression Kinetics Analysis (RPKA) uses in situ data under synthetically relevant concentrations and captures information throughout the whole experiment ensuring that the complete reaction behavior can be accurately described.

Understand and Control Grignard Reaction Development and Scale-up With Process Analytical Technology

Exothermic chemical reactions pose inherent risks, especially during scale-up. Risks include safety hazards, such as excessive pressure, contents discharge, or explosion, as well as product yield and purity degradation associated with any sharp temperature rise. For example, inadequate control of Grignard reactions introduces safety concerns associated with the accumulation of the organic halide which, if undetected, can result in a catastrophic event leading to a runaway reaction.

Understand and Optimize Effects of Process Parameters on Hydrogenation Reactions

Studying hydrogenation reactions requires informed decisions to optimize the process in the laboratory and ensure it is repeatable on scale up. Continuous, real-time reaction measurements are applied to gain deep, fundamental process understanding. This is applied to make faster decisions to reduce the number of experiments and the time to scale-up the process; to increase selectivity/yield from almost instantaneous feedback on the direction of the reaction; to reduce cycle time and improve yield by determining the ideal endpoint by stopping a reaction at a specific time point and avoiding the risk of a byproduct formation.

Highly reactive chemistry is a terminology used to describe chemical reactions that are particularly challenging to handle and develop due to the potentially hazardous and/or energetic nature of the reactants, intermediates and products that are present during synthesis. These chemistries often involve highly exothermic reactions which require specialized equipment or extreme operating conditions (such as low temperature) to ensure adequate control. Ensuring safe operating conditions, minimizing human exposure, and gaining the maximum amount of information from each experiment are key factors in successfully designing and scaling-up highly reactive chemistries.

Particularly challenging is the fact that sampling the reactor contents during the reaction is often impractical or impossible under the desired operating conditions. In addition, as highly reactive materials are often unstable, the accuracy of any possible offline analysis is often limited.

Handling of reagents can be minimized through the use of synthesis workstations, a new generation of technology, that are designed to provide high quality synthetic conditions (such as control over temperature and pH), a degree of automation of methods, and importantly greatly reduce the amount of material that comes into contact with the operator.

The sampling challenge can be addressed through the use of in situ reaction monitoring technology such as ReactIR™. This technology allows scientists to design and develop better and safer processes through the delivery of information regarding the behavior of reaction species such as starting materials, intermediates and products, allowing them to gain a greater understanding of the reaction being studied.

Continuous flow chemistry opens options with exothermic synthetic steps that are not possible in batch reactors, and new developments in flow reactor design provide alternatives for reactions that are mixing limited in batch reactors. This can often result in better product quality and higher yield. When coupled with Process Analytical Technology (PAT), flow chemistry allows for rapid analysis, optimization, and scale-up of a chemical reaction.

Measuring and understanding polymerization reactions, mechanisms, kinetics, reactivity ratios, and activation energies lead researchers to employ in situ infrared spectroscopy as a routine technique to gain comprehensive, information-rich data that is used to advance research in a shorter time frame.

Optimization and scale-up of crystallization and precipitation to produce a product that consistently meets purity, yield, form and particle size specifications can be one of the biggest challenges of process development.

Risks of Explosions in Chemical Process and How to Avoid Hazards in the Plant

Scientists and engineers eliminate risks of explosions in a chemical plant with a comprehensive safety study. The safety study is applied to develop a process that eliminates uncontrolled heat or gas generation, flammable vapor release, or an over-pressurization of the reactor leading to rupture and loss of contents, which may be flammable. In order to avoid the risk of uncontrolled heat generation, reaction calorimetry determines the heat of reaction and the rate of heat release, so that a process can be designed that minimizes the risk of loss of control.

Essential measurements and calculations are necessary to model runaway scenarios and establish the ideal reaction procedure. Measuring, calculating, and understanding the parameters are essential to assess and avoid risk in a chemical process. This allows scientists to make predictions about the temperature profiles, maximum operating temperature, and dosing.

The heat of reaction, or reaction enthalpy, is an essential parameter to safely and successfully scale-up chemical processes. The heat of reaction is the energy that is released or absorbed when chemicals are transformed in a chemical reaction.

Scaling-up a chemical process from lab to manufacturing gives useful results only with accurate heat transfer coefficients. Measuring the jacket and reactor temperature (during the release of a well-defined amount of heat) allows researchers to accurately compute the thermal resistance which is used to model the heat transfer and make critical predictions for reactors at larger scale. Reaction calorimetry is essential to determine parameters that impact the heat transfer and the heat transfer coefficients to develop models to maximize the bandwidth of a manufacturing plant.

Mixing is the reduction or elimination of inhomogeneity of phases that are either miscible or immiscible. Process scale-up and optimization require that the impact of mixing on the reaction rate be quantified. Automated, controlled experiments can be run in parallel in a laboratory reactor system to establish a mass transfer correlation, and provide a means to quickly adjust the gas/ liquid interface area and reactor volume. This achieves the desired conditions required for the scale-up or scale-down of a process.

In situ chemical reaction kinetics studies provide an improved understanding of reaction mechanism and pathway by providing concentration dependences of reacting components in real-time. Continuous data over the course of a reaction allows for the calculation of rate laws with fewer experiments due to the comprehensive nature of the data. Reaction Progression Kinetics Analysis (RPKA) uses in situ data under synthetically relevant concentrations and captures information throughout the whole experiment ensuring that the complete reaction behavior can be accurately described.

Exothermic chemical reactions pose inherent risks, especially during scale-up. Risks include safety hazards, such as excessive pressure, contents discharge, or explosion, as well as product yield and purity degradation associated with any sharp temperature rise. For example, inadequate control of Grignard reactions introduces safety concerns associated with the accumulation of the organic halide which, if undetected, can result in a catastrophic event leading to a runaway reaction.

Studying hydrogenation reactions requires informed decisions to optimize the process in the laboratory and ensure it is repeatable on scale up. Continuous, real-time reaction measurements are applied to gain deep, fundamental process understanding. This is applied to make faster decisions to reduce the number of experiments and the time to scale-up the process; to increase selectivity/yield from almost instantaneous feedback on the direction of the reaction; to reduce cycle time and improve yield by determining the ideal endpoint by stopping a reaction at a specific time point and avoiding the risk of a byproduct formation.

Highly reactive chemistry is a terminology used to describe chemical reactions that are particularly challenging to handle and develop due to the potentially hazardous and/or energetic nature of the reactants, intermediates and products that are present during synthesis. These chemistries often involve highly exothermic reactions which require specialized equipment or extreme operating conditions (such as low temperature) to ensure adequate control. Ensuring safe operating conditions, minimizing human exposure, and gaining the maximum amount of information from each experiment are key factors in successfully designing and scaling-up highly reactive chemistries.

Particularly challenging is the fact that sampling the reactor contents during the reaction is often impractical or impossible under the desired operating conditions. In addition, as highly reactive materials are often unstable, the accuracy of any possible offline analysis is often limited.

Handling of reagents can be minimized through the use of synthesis workstations, a new generation of technology, that are designed to provide high quality synthetic conditions (such as control over temperature and pH), a degree of automation of methods, and importantly greatly reduce the amount of material that comes into contact with the operator.

The sampling challenge can be addressed through the use of in situ reaction monitoring technology such as ReactIR™. This technology allows scientists to design and develop better and safer processes through the delivery of information regarding the behavior of reaction species such as starting materials, intermediates and products, allowing them to gain a greater understanding of the reaction being studied.

Continuous flow chemistry opens options with exothermic synthetic steps that are not possible in batch reactors, and new developments in flow reactor design provide alternatives for reactions that are mixing limited in batch reactors. This can often result in better product quality and higher yield. When coupled with Process Analytical Technology (PAT), flow chemistry allows for rapid analysis, optimization, and scale-up of a chemical reaction.

Measuring and understanding polymerization reactions, mechanisms, kinetics, reactivity ratios, and activation energies lead researchers to employ in situ infrared spectroscopy as a routine technique to gain comprehensive, information-rich data that is used to advance research in a shorter time frame.

Optimization and scale-up of crystallization and precipitation to produce a product that consistently meets purity, yield, form and particle size specifications can be one of the biggest challenges of process development.

Scientists and engineers eliminate risks of explosions in a chemical plant with a comprehensive safety study. The safety study is applied to develop a process that eliminates uncontrolled heat or gas generation, flammable vapor release, or an over-pressurization of the reactor leading to rupture and loss of contents, which may be flammable. In order to avoid the risk of uncontrolled heat generation, reaction calorimetry determines the heat of reaction and the rate of heat release, so that a process can be designed that minimizes the risk of loss of control.

Essential measurements and calculations are necessary to model runaway scenarios and establish the ideal reaction procedure. Measuring, calculating, and understanding the parameters are essential to assess and avoid risk in a chemical process. This allows scientists to make predictions about the temperature profiles, maximum operating temperature, and dosing.

The heat of reaction, or reaction enthalpy, is an essential parameter to safely and successfully scale-up chemical processes. The heat of reaction is the energy that is released or absorbed when chemicals are transformed in a chemical reaction.

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